The broad objective of this research program is to expand our understanding of bile formation. We are interested in the normal physiology of this process as well as in the mechanisms of biliary disease. To these ends we will study the transport kinetics of representative organic solutes by compartmental analysis, explore the use of cultured liver cells to analyze the canalicular transport of H20 and inorganic ions, and study the mechanism of action of SC-2644, a potent bile acid-independent choleretic. Each of these experimental approaches will be applied subsequently to a study of experimental cholestasis induced by ethinyl estradiol. The experimental subjects in each case are common laboratory animals.